多因素大鼠肝癌综合模型的建立与药物验证  

Establishment of A Multifactorial Comprehensive Model of Liver Cancer in Rat and Verification of the Model Using Chinese and Western Medicines

作　　者：倪峰[1] 张月芬[1] 黄慧[1] 郭丹[1] 戴雅彬 洪雅娟 郑妙兰 覃美玲 张珊瑜 NI Feng;ZHANG Yuefen;HUANG Hui;GUO Dan;DAI Yabin;HONG Yajuan;ZHENG Miaolan;QIN Meiling;ZHANG Shanyu(Fujian Health College,Fuzhou 350101 Fujian,China)

机构地区：[1]福建卫生职业技术学院,福建福州350101

出　　处：《中药新药与临床药理》2022年第9期1242-1247,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：福建省科技厅社会发展引导性(重点)项目(2019Y0051);福建卫生职业技术学院应用技术协同创新研究重点项目(2018-2-3)。

摘　　要：目的 在经典化学诱癌模型的基础上,施加农药残留、高脂高糖饮食、湿热环境3因素,构建多因素大鼠肝癌综合模型,并考察中西药物对该模型的影响。方法 将大鼠按体质量随机分为正常对照组、二乙基亚硝铵(DEN)模型组、综合模型组、西药组和中药组。除正常对照组外,其余各实验组大鼠自由饮用DEN水。综合模型组大鼠除给予DEN外,自由摄食高脂高糖饲料,皮下注射0.5 mg·kg^(-1))灭多威溶液,每周1次;每隔1 d于人工气候箱中进行湿热处理(湿热条件:温度30℃,湿度90%,每次30 min)。西药组大鼠在综合模型造模基础上,第9周开始腹腔注射氟尿嘧啶30 mg·kg^(-1)),每周1次,共治疗7周。中药组大鼠在综合模型造模基础上第4周开始腹腔注射康艾注射液3 mL·kg^(-1)),每周1次,共治疗12周。15周后观察各组大鼠体质量、肝质量、肝脏指数、肝表面癌结节数及成瘤率,并对肝脏进行病理组织学检查;全自动生化分析仪检测血清谷丙转氨酶(ALT)和谷草转氨酶(AST)的含量;Elisa法检测甲胎蛋白(AFP)和磷脂酰肌醇蛋白聚糖3(GPC-3)的表达。结果 与正常对照组相比,综合模型组大鼠体质量明显降低,肝质量和肝脏指数明显增加,血清ALT、AST、AFP和GPC-3活性升高,差异有统计学意义(P<0.05);与DEN模型组比较,综合模型组体质量明显降低,肝质量和肝脏指数明显增加,血清ALT、AST活性增加,差异有统计学意义(P<0.05);与综合模型组比较,中、西药治疗组大鼠各项指标均得到明显改善,差异有统计学意义(P<0.05)。肝脏组织形态学显示综合模型组的癌变特征比DEN模型组更明显。结论 多因素大鼠肝癌综合模型相对于经典的化学诱癌模型更贴近临床肝癌的症状与病理特征,并能体现中西抗癌药物的治疗效果。Objective To establish a comprehensive model of rat liver cancer by imposing pesticide residues,highfat and high-sugar diet,and humid-heat environment on the base of the liver cancer model induced by chemical reagents, and observe the effects of the Chinese and western medicines on this model. Methods The rats were randomly divided into normal control group,diethylnitrosamine(DEN)model group,comprehensive model group,chemotherapy drug group and Chinese medicine group. Except for the normal control group, the rats in each modeling group drank DEN water freely. In addition to DEN water,the rats in the comprehensive modeling group ate high-fat and high-sugar diet freely,and were injected subcutaneously with 0.5 mg·kg^(-1))methomyl solution once a week, and the rats were put into an artificial climate machine for humid-heat treatment(treatment conditions:temperature 30 ℃,humidity 90%,30 minutes each time)every other day. The rats in the chemotherapy drug group were given intraperitoneal injection of Fluorouracil(30 mg·kg^(-1))once a week)from the ninth week of the experiment for 7 weeks. Rats in the traditional Chinese medicine group were injected with Kangai Injection(3 mL·kg^(-1)),once a week)by intraperitoneal injection from the fourth week of the experiment for 12 weeks. Fifteen weeks later, the tumor formation rate,body mass,liver mass,liver index,and the number of cancer nodules on the liver surface of the rats in each group were observed, and histopathological examination of the livers was performed. The serum contents of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected by automatic biochemical analyzer. ELISA was used to detect the expression of alpha-fetoprotein(AFP)and phosphatidylinositol proteoglycan 3(GPC-3). Results Compared with the normal control group,the rats’ body mass in the comprehensive model group was significantly decreased, the liver mass and liver index were significantly increased, and the activities of serum ALT, AST, AFP, and GPC-3 were increased too,

关 键 词：大鼠 肝癌 二乙基亚硝胺 农药残留 高脂高糖饮食 湿热环境 氟尿嘧啶 康艾注射液 

分 类 号：R285.5[医药卫生—中药学]